Overexpression of blaGES-1 due to a strong promoter in the class 1 integron contributes to decreased ceftazidime-avibactam susceptibility in carbapenem-resistant Pseudomonas aeruginosa ST235

Li, Xi; Zhang, Xiaofan; Cai, Heng; Zhu, Yiwei; Ji, Jingshu; Qu, Tingting; Tu, Yuexing; Zhou, Hua; Yu, Yunsong

doi:10.1016/j.drup.2023.100973

Cited by 7 publications

(7 citation statements)

References 18 publications

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“…Fourteen XDR-hvPA strains were classified into A clone cluster. These had the closest similarity to JAPZLY01, which were obtained from Hangzhou, Zhejiang, in a previous report by Li et al [ 14 ], with an SNP difference of 1–5 (except for P51 and P87), indicating that ST235 P. aeruginosa may have clonal transmission in China and should be highly valued. (Fig.…”

Section: Resultsmentioning

confidence: 53%

“…Thus far, 206 strains of ST235 P. aeruginosa have been uploaded to the system globally. In addition, we conducted homology analysis on these 206 strains of ST235 P. aeruginosa , 15 strains of ST235 P. aeruginosa from Hangzhou, Zhejiang, which were previously reported by Li et al [ 14 ], and 14 strains of XDR-hvPA reported in this study. The results showed that these 235 strains could be divided into 11 clusters, with clusters A, B, C, and D being the most prevalent, accounting for 98.3% of all strains, indicating clonal transmission.…”

Section: Resultsmentioning

confidence: 89%

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Molecular characterization of extensively drug-resistant hypervirulent Pseudomonas aeruginosa isolates in China

Li,

Tang,

Liu

et al. 2024

Ann Clin Microbiol Antimicrob

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Background Recently, extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) isolates have been increasingly detected and posed great challenges to clinical anti-infection treatments. However, little is known about extensively resistant hypervirulent P. aeruginosa (XDR-hvPA). In this study, we investigate its epidemiological characteristics and provide important basis for preventing its dissemination. Methods Clinical XDR-PA isolates were collected from January 2018 to January 2023 and identified using matrix-assisted laser desorption/ionization–time-of-flight mass spectrometry; antibiotic susceptibility testing was performed by broth microdilution method, and minimum inhibitory concentrations (MICs) were evaluated. Virulence was evaluated using the Galleria mellonella infection model; molecular characteristics, including resistance genes, virulence genes, and homology, were determined using whole-genome sequencing. Results A total of 77 XDR-PA strains were collected; 47/77 strains were XDR-hvPA. Patients aged > 60 years showed a significantly higher detection rate of XDR-hvPA than of XDR-non-hvPA. Among the 47 XDR-hvPA strains, 24 strains carried a carbapenemase gene, including blaGES−1 (10/47), blaVIM−2 (6/47), blaGES−14 (4/47), blaIMP−45 (2/47), blaKPC−2 (1/47), and blaNDM−14 (1/47). ExoU, exoT, exoY, and exoS, important virulence factors of PA, were found in 31/47, 47/47, 46/47, and 29/47 strains, respectively. Notably, two XDR-hvPA simultaneously co-carried exoU and exoS. Six serotypes (O1, O4–O7, and O11) were detected; O11 (19/47), O7 (13/47), and O4 (9/47) were the most prevalent. In 2018–2020, O4 and O7 were the most prevalent serotypes; 2021 onward, O11 (16/26) was the most prevalent serotype. Fourteen types of ST were detected, mainly ST235 (14/47), ST1158 (13/47), and ST1800 (7/47). Five global epidemic ST235 XDR-hvPA carried blaGES and showed the MIC value of ceftazidime/avibactam reached the susceptibility breakpoint (8/4 mg/L). Conclusions The clinical detection rate of XDR-hvPA is unexpectedly high, particularly in patients aged > 60 years, who are seemingly more susceptible to contracting this infection. Clonal transmission of XDR-hvPA carrying blaGES, which belongs to the global epidemic ST235, was noted. Therefore, the monitoring of XDR-hvPA should be strengthened, particularly for elderly hospitalized patients, to prevent its spread.

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Section: Resultsmentioning

confidence: 53%

Section: Resultsmentioning

confidence: 89%

Molecular characterization of extensively drug-resistant hypervirulent Pseudomonas aeruginosa isolates in China

Li,

Tang,

Liu

et al. 2024

Ann Clin Microbiol Antimicrob

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“…In PA strains, resistance to CZA is primarily associated with β-lactam enzyme mutations, structural modifications, and increased efflux pump expression, aside from MBL-positive strains [ 43 ]. Notably, β-lactam enzyme mutations have become the primary contributing factor to CZA resistance in PA. Several reports, including two from our group, have shown that different β-lactam enzyme mutant genes, such as bla OXA-10 [ 44 ], bla GES-15 [ 45 ], bla KPC-33 [ 18 ] and bla KPC-90 [ 16 ], confer resistance to CZA in PA. Additionally, the overexpression of β-lactam enzymes such as KPC-2, AmpC, PER-1 and GES-1, has been associated with reduced susceptibility to CZA in PA [ 15 , 17 , 19 , 46 , 47 ]. It is important to note that previous studies have shown that these factors contribute to a low level of CZA resistance.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, it is worth noting that different PA strains may employ different efflux systems to achieve the same goal. We previously found that overexpression of KPC-90 and MexXY-OprM efflux pumps [ 16 ] as well as overexpression of the efflux pumps MexAB-OprM and GES-1 both conferred in directing CZA resistance [ 19 ]. Our results showed that MexAB-OprM , MexEF-OprN and MexXY-OprM expression were significantly increased in the CZA high-level resistance isolates.…”

Section: Discussionmentioning

confidence: 99%

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Genomic epidemiology and ceftazidime-avibactam high-level resistance mechanisms of Pseudomonas aeruginosa in China from 2010 to 2022

Li,

Zhou,

Lei

et al. 2024

Emerging Microbes & Infections

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Ceftazidime-avibactam (CZA) resistance is a huge threat in the clinic; however, the underlying mechanism responsible for high-level CZA resistance in Pseudomonas aeruginosa (PA) isolates remains unknown. In this study, a total of 5,763 P. aeruginosa isolates were collected from 2010 to 2022 to investigate the ceftazidime-avibactam (CZA) high-level resistance mechanisms of Pseudomonas aeruginosa (PA) isolates in China. Fifty-six PER-producing isolates were identified, including 50 isolates carrying bla PER-1 in PA, and 6 isolates carrying bla PER-4 . Of these, 82.1% (46/56) were classified as DTR-PA isolates, and 76.79% (43/56) were resistant to CZA. Importantly, bla PER-1 and bla PER-4 overexpression led to 16-fold and >1024-fold increases in the MICs of CZA, respectively. WGS revealed that the bla PER-1 gene was located in two different transferable IncP-2-type plasmids and chromosomes, whereas bla PER-4 was found only on chromosomes and was carried by a class 1 integron embedded in a Tn 6485 -like transposon. Overexpression of efflux pumps may be associated with high-level CZA resistance in bla PER-1 -positive strains. Kinetic parameter analysis revealed that PER-4 exhibited a similar kcat / Km with ceftazidime and a high (∼3359-fold) IC50 value with avibactam compared to PER-1. Our study found that overexpression of PER-1 combined with enhanced efflux pump expression and the low affinity of PER-4 for avibactam contributes to high-level resistance to CZA. Additionally, the Tn 6485 -like transposon plays a significant role in disseminating bla PER . Urgent active surveillance is required to prevent the further spread of high-level CZA resistance in DTR-PA isolates.

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Metagenomic analysis unveiled the response of microbial community and antimicrobial resistome in natural water body to duck farm sewage

Fang,

Liu,

Tian

et al. 2024

Environmental Pollution

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Overexpression of blaGES-1 due to a strong promoter in the class 1 integron contributes to decreased ceftazidime-avibactam susceptibility in carbapenem-resistant Pseudomonas aeruginosa ST235

Cited by 7 publications

References 18 publications

Molecular characterization of extensively drug-resistant hypervirulent Pseudomonas aeruginosa isolates in China

Molecular characterization of extensively drug-resistant hypervirulent Pseudomonas aeruginosa isolates in China

Genomic epidemiology and ceftazidime-avibactam high-level resistance mechanisms of Pseudomonas aeruginosa in China from 2010 to 2022

Metagenomic analysis unveiled the response of microbial community and antimicrobial resistome in natural water body to duck farm sewage

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